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Short- and Long-term Evaluation of Bioresorbable Scaffolds by Optical Coherence Tomography
Short- and Long-term Evaluation of Bioresorbable Scaffolds by Optical Coherence Tomography Carlos M. Campos, MDa,b, Pannipa Suwannasom, MDa, Shimpei Nakatani, MDa, Yoshinobu Onuma, MD, PhDa, Patrick W. Serruys, MD, PhDa,c, Hector M. Garcia-Garcia, MD, PhDa,d,* KEYWORDS Bioresorbable scaffolds Optical coherence tomography Drug-eluting stents
KEY POINTS The analysis of bioresorbable scaffolds (BRSs) by optical coherence tomography (OCT) requires a dedicated methodology, as the polymeric scaffold has a distinct appearance and undergoes dynamic structural changes with time, unlike metallic stents. The high resolution of OCT allows for the detailed assessment of scaffold implantation, rupture, discontinuity, and strut integration. OCT does not provide reliable information on the extent of scaffold degradation, as it cannot differentiate between polylactide polymer and the provisional matrix of proteoglycan formed by connective tissue. Three-dimensional OCT reconstruction can aid in the evaluation of BRS in special scenarios such as overlapping scaffold segments and bifurcations.
INTRODUCTION BRSs represent a novel approach in the treatment of coronary artery disease. They support the vessel transiently to maintain patency after intervention, deliver antiproliferative drug to the vessel wall, and then gradually degrade.1,2 BRS technology has matured, and there are numerous devices that are commercially available outside the United States or are undergoing preclinical or clinical evaluation (Fig. 1). BRS has required new imaging modalities, methodologies, and strategies, because
scaffold design, degradation rate, loss of mechanical properties (Table 1), coating, and drug deliverability may affect BRS safety and efficacy.3,4 OCT has played a central role in understanding the short and long term BRS performance, OCT provides more detailed and precise morphologic information about BRS than does intravascular ultrasonography (IVUS) because of its higher resolution.5,6 This review summarizes the methodology and clinical application of OCT in the assessment of BRS, in particular for the commercially available Absorb Bioresorbable
The authors have nothing to disclose. a Department of Interventional Cardiology, Thoraxcenter, Erasmus University Medical Centre, Dr. Molewaterplein 40, Rotterdam 3015 GD, The Netherlands; b Department of Interventional Cardiology Heart Institute (InCor), University of Sa˜o Paulo Medical School, Avenida Doutor Ene´as de Carvalho Aguiar, 44 - Terceiro Andar, Sao Paulo 05403-900, Brazil; c International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; d Medical Affairs, Cardialysis, Westblaak 98, Entrance B, Rotterdam 3012 KM, The Netherlands * Corresponding author. Westblaak 98, Entrance B, Rotterdam 3012 KM, The Netherlands. E-mail address: [email protected] Intervent Cardiol Clin 4 (2015) 333–349 http://dx.doi.org/10.1016/j.iccl.2015.03.001 2211-7458/15/$ – see front matter ª 2015 Elsevier Inc. All rights reserved.
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Fig. 1. Optical coherence tomography images of different bioresorbable vascular scaffolds. Absorb BVS 1.1 (Abbott Vascular, Santa Clara, CA, USA); Fortitude (Amaranth Medical, Mountain View, CA, USA); DESolve BRS (Elixir, Sunnyvale, CA, USA); DREAMS 1.0 absorbable metallic scaffold (Biotronik, Berlin, Germany); Ideal II BioStent (Xenogenics, Philadelphia, PA, USA); Igaki-Tamai scaffold (Kyoto Medical Planning Co, Kyoto, Japan); On-AVS (Orbus Neich, Wanchai, Hong Kong); REVA (REVA Medical Inc, San Diego, CA, USA). An OCT image for IgakiTamai was not available at baseline.
Table 1 Mechanical properties and degradation rate of different material candidates for bioresorbable coronary scaffolds
a
Material
Tensile Strength (MPa)
Elongation (%)
Degradation Time
Poly(L-lactide)
60–70
2–6
24 moa
Poly(DL-lactide)
45–55
2–6
12–16 moa
Poly(glycolide)
90–110
1–2
6–12 moa
50/50
40–50
1–4
1–2 moa
82/18 L-lactide/glycolide
60–70
2–6
12–18 moa
70/30 L-lactide/ε-aprolactone
18–22
>100
12–24 moa
DL-lactide/glycolide
Pure Fe
200
40
0.19 mm/y
Fe-35 Mn alloy
430
30
0.44 mm/y
WE43 alloy
280
2
1.35 mm/y
Degradation time depends on geometry. Data from Moravej M, Mantovani D. Biodegradable metals for cardiovascular stent application: interests and new opportunities. Int J Mol Sci 2011;12:4250–70; and van Alst M, Eenink MJ, Kruft MA, et al. ABC’s of bioabsorption: application of lactide based polymers in fully resorbable cardiovascular stents. EuroIntervention 2009;5(Suppl F):F23–7.
OCT for Bioresorbable Scaffolds Assessment
Vascular Scaffold (BVS) (Abbot Vascular, Santa Clara, CA, USA), as this device had the most extensive short- and long-term follow-up data.
RATIONALE FOR THE NEED FOR A DEDICATED ANALYSIS METHODOLOGY FOR THE OPTICAL COHERENCE TOMOGRAPHIC ASSESSMENT OF BIORESORBABLE SCAFFOLDS The OCT appearance of polymeric scaffolds differs significantly from that of metallic scaffolds and stents (Fig. 2A). The appearance of magnesium scaffolds immediately after implantation is similar to that of a permanent metallic stent, that is, a bright strut with well-delimited borders with a shadow behind (see Fig. 2A). In contradistinction, polymeric struts are optically translucent and appear as a black central core framed by light-scattering borders that do not shadow the vessel wall, and therefore the complete thickness of the scaffold strut can be visualized (see Fig. 2B). The main quantitative measurements for scaffold evaluation by OCT include strut core area, strut area, lumen area, scaffold area, incomplete strut apposition (ISA) area, and neointimal area. Because polymeric scaffolds scatter light differently and have different OCT characteristics than metallic stents/scaffolds (see Fig. 2B, C), these measurements must be acquired using different image analysis rules.
OPTICAL COHERENCE TOMOGRAPHIC EVALUATION OF BIORESORBABLE SCAFFOLDS AT TIME OF IMPLANTATION Several OCT parameters can be collected at the time of short-term implantation of the BRS; these are summarized in Table 2. Key quantifications include the lumen and scaffold areas, the magnitude of ISA, lumen prolapse, and flow area. The high resolution provided by OCT also allows the operator to visualize the quality of scaffold implantation and the potential complications related to it. Important analyses include assessments of short-term strut fracture, edge dissection, eccentricity, and symmetry.
Contours At baseline, the lumen and scaffold contours are obtained with a semiautomated detection algorithm available in numerous off-line software packages. These contours can be corrected manually if necessary. Lumen and Scaffold Areas Because the polymeric struts are translucent, the vessel lumen border can be visualized and the
vessel lumen area delineated along the external (abluminal) side of the struts. The scaffold area is measured by joining the internal middle points of the abluminal side of the black cores of the apposed struts or the abluminal edge of the frame borders of malapposed struts. In the absence of ISA and plaque prolapse, the scaffold area is identical to the lumen area (see Fig. 2C).
Incomplete Strut Apposition ISA is defined by a clear separation between the abluminal side of the strut and the vessel wall. ISA area is delineated by the abluminal side of the frame border of the malapposed struts and the endoluminal contour of the lumen. Lumen Prolapse Several different parameters can be collected in the case of lumen or plaque prolapse protruding between the struts into the lumen. The prolapse area can be estimated by the planimetered difference between the prolapsed contour (ie, lumen contour) and the scaffold area. An intraluminal defect that is separated from the vessel wall (eg, thrombus) can also be quantified as an area. Flow Area Flow area takes into account ISA, plaque prolapse, and intraluminal defects. It is defined as the difference between the sum of the scaffold and ISA areas and the sum of the areas of intraluminal struts, prolapse, and intraluminal defect (ie, flow area 5 [scaffold area 1 ISA area] [intraluminal strut areas 1 prolapse area 1 intraluminal defect area]). Short-term Strut Fracture The diagnosis of short-term strut fracture due to balloon overdilation can be established if 2 struts overhang each other within the same angular sector of the lumen perimeter (Fig. 3). This complication may be observed with or without concomitant strut malapposition. However, if isolated struts are located more or less at the center of the vessel without an obvious connection with other surrounding struts, strut fracture may also be present. It is helpful to perform 3-dimensional reconstruction of the OCT dataset to confirm the diagnosis. Edge Dissection Edge dissection is defined by OCT as the disruption of the endoluminal vessel surface at the proximal and distal edges of the BRS (Fig. 4).7 In the ABSORB Cohort B trial, 24% of patients had proximal and 42% had distal edge dissection flaps postprocedure.8 On follow-up, proximal and distal edge dissection flaps seem to
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Fig. 2. (A) Representative optical coherence tomographic image of the drug-eluting absorbable metal scaffold DREAMS (Biotronik, Bu¨lach, Switzerland) immediately after implantation looks like a permanent metallic stent (left). Absorb BVS has optically translucent struts and appears as a black central core framed by light-scattering borders that do not shadow the vessel wall and allow complete imaging of the strut thickness (right). (B) Methodology for the assessment of incomplete scaffold apposition (ISA) with the drug-eluting absorbable metal scaffold DREAMS. (C) Newly implanted bioresorbable scaffold. Differences in the methodology of OCT assessment between metallic stents and BVS are illustrated. Panel 1. Metallic stent approach. Note that with metallic scaffold/stent analysis, device area is calculated by planimetry of the endoluminal border of the struts. Lumen area, 10.16 mm2; stent area, 7.84 mm2, ISA, 2.32 mm2. Panel 2. BVS approach. Lumen area, 10.16 mm2; stent area, 9.58 mm2; ISA, 0.58 mm2. Panel 3. Additional BVS analyses. Strut area, 0.61 mm2; blood flow area (lumen area strut area), 9.55 mm2. Panel 4. Follow-up OCT imaging of BVS. Strut area is defined only by its black core, because the light-scattering frame is no longer distinguishable from the surrounding tissue. Neointimal area is defined by (scaffold area lumen area strut area). ([C] Adapted from Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
OCT for Bioresorbable Scaffolds Assessment
Table 2 Definitions and formulas for the quantification of OCT parameters for the assessment of BRSs Parameter
Formula
Definition and Notes
Eccentricity index
Minimum scaffold diameter/maximum scaffold diameter in a frame
The average of all eccentricity indices of each frame within scaffolded segment is calculated
Symmetry index
(Minimum scaffold diameter maximum scaffold diameter)/ maximum scaffold diameter within a scaffolded segment
The maximum and the minimum stent/scaffold diameters in this calculation were possibly located in 2 different frames along the length of the device implanted
Scaffold area
At baseline, the scaffold area is measured by joining the middle points of the abluminal sides of the black cores of the apposed struts or the abluminal edge of the frame borders of malapposed struts. At follow-up, the abluminal side of the central black core is used to delimit the scaffold area
Blood flow area
(Scaffold area 1 ISA area) (intraluminal strut areas 1 prolapse area 1 intraluminal defect area)
Neointimal hyperplasia area
i. In case of all struts apposed Scaffold area [lumen area 1 black box area] ii. In case of malapposed struts [Scaffold area 1 ISA area 1 malapposed strut with surrounding tissues] [lumen area 1 strut area]
Note the difference of methodology with that of gray-scale IVUS
Thickness of tissue coverage
Distance between the abluminal site of the strut and the lumen strut thickness
Since the strut thickness is 150 mm (ABSORB), the strut was considered as covered whenever the thickness of the coverage was more than this threshold value. This method may slightly underestimate the thickness of the coverage because it does not take into account changes in the size of the strut core over time
Adapted from Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.
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Fig. 3. Representative OCT image of scaffold fracture and discontinuity. (A) Scaffold fracture. During the index procedure after postdilatation of an Absorb BVS, OCT cross-sectional image shows scaffold fracture (blue arrow, left). The strut luminal and abluminal surfaces are no longer orientated perpendicular to the light source. OCT crosssectional image 1 month later shows extensive strut disarray (dotted blue arrow, right). (B) Scaffold discontinuity. OCT acquisition 6 months after Absorb BVS implantation. In the 2-dimensional (cross-sectional) OCT image, extreme malapposition of 1 strut is seen (panel B2, yellow arrow). In the 3-dimensional reconstruction, the overhanging strut is clearly identified in its whole trajectory (panel B3, B4; yellow arrow). Further intervention was deferred because of lack of ischemic symptoms. ([A] Adapted from Ormiston JA, De Vroey F, Serruys PW, et al. Bioresorbable polymeric vascular scaffolds: a cautionary tale. Circ Cardiovasc Interv 2011;4:535– 8; and [B] From Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
have resolved. In serial OCT analysis of BRSs, postprocedural proximal edge dissection was noted in 21% of cases and distal edge dissection in 38% of cases, compared with 2% and 5% at 6 months, respectively. At 1 year, an edge dissection was present in only 2% (proximal) and none were observed at 2- and 3-year follow-up. No scaffold thrombosis was reported in this trial.8 Therefore, although edge dissection by OCT is often detected, most of these dissections healed within 6 months without any clinical
sequelae. However, the small sample size of this study limits any definitive conclusion with respect to the effect of residual edge dissection on clinical outcomes.
Eccentricity and Symmetry The eccentricity and symmetry of implanted BRSs are easily assessed by OCT (see Table 2). These parameters have been shown to be associated with clinical outcomes after metallic stents.9,10 With the clinical adoption of various
OCT for Bioresorbable Scaffolds Assessment
Fig. 4. Representative imaging of a dissection at the distal edge of Absorb BVS. (A) Longitudinal view of a distal dissection. (B) Three-dimensional reconstruction of OCT pullback showing luminal disruption at distal edge of the scaffold (double white arrow). (C, D) Three-dimensional reconstruction at 6-month and 2-year follow-up, respectively, demonstrating that the dissection has healed. (E) No distal edge dissection is visible from the angiograms postprocedure (yellow arrow). (F) OCT cross-sectional images immediately after implantation show that a dissection extends into the media. (G) OCT image at 6-month follow-up demonstrates an increase in lumen area at that region without visible dissection. (H) At 2-year follow-up, the lumen area has decreased with detected calcific tissue. Asterisk, side branch. (From Zhang YJ, Iqbal J, Nakatani S, et al. ABSORB Cohort B Study Investigators. Scaffold and edge vascular response following implantation of everolimus-eluting bioresorbable vascular scaffold: a 3 year serial optical coherence tomography study. JACC Cardiovasc Interv 2014;7(12):1361–9.)
bioresorbable devices, the reevaluation of the clinical effect of these geometric parameters is required at short- and long-term follow-up. The eccentricity ratio is defined as the ratio of the minimum and maximum diameters of the scaffold in each frame. The eccentricity index is obtained by calculating the average of all eccentricity ratios along the length of the scaffold.3 The symmetry index is derived from the maximum scaffold diameter and minimum scaffold diameter along the length of the BRS, which may be located within different frames. It is calculated as the difference between the maximum scaffold diameter and the minimum scaffold diameter, divided by the maximum scaffold diameter.3 It must be emphasized that the maximum and the minimum scaffold diameters
in this calculation may be located in 2 different frames along the length of the implanted device (Fig. 5).
Bioresorbable Scaffold Versus Drug-Eluting Stent at Time of Implantation BRSs have distinct mechanical properties compared with metallic stents that could influence the aforementioned OCT parameters. Mattesini and colleagues11 compared the final, postimplantation results of the Absorb BVS and second-generation drug-eluting stents (DESs) using OCT. A total of 50 complex coronary lesions (class B2/C by the American College of Cardiology/American Heart Association definition) treated with a BVS undergoing a final OCT examination were compared with an equal
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Fig. 5. Definition of the symmetry and eccentricity indices according to OCT. Minimum and maximum diameters along the length of the device are shown. Two cross-sections with different eccentricity indices are also shown.
number of matched lesions treated with second-generation DESs. In the BRS group, there was more extensive lesion preparation (eg, significantly greater balloon diameter:reference vessel diameter ratio and higher inflation predilation pressure) and significantly higher postdilatation pressure used. Final OCT examination demonstrated a trend toward greater tissue prolapse area (P 5 .08) and a significantly higher rate of proximal edge ISA (P 5 .04) in the BVS group. There was no significant difference in the overall ISA, mean lumen area, and eccentricity index between the 2 groups. There
were 2 cases of strut fractures in the lesions treated with BVS, whereas none was observed with DES.11
OPTICAL COHERENCE TOMOGRAPHIC EVALUATION OF BIORESORBABLE SCAFFOLD OVER LONG-TERM FOLLOW-UP Because BRSs are designed to degrade with time after implantation, the structural characteristics of the scaffold are dynamic and can be well visualized by OCT imaging. Key parameters that may
OCT for Bioresorbable Scaffolds Assessment
be assessed during ongoing follow-up include the presence of any scaffold discontinuity, scaffold eccentricity, strut coverage, and neointimal hyperplasia.
surrounding tissues (ie, [scaffold area 1 ISA area 1 malapposed strut with surrounding tissues] [lumen area 1 strut area]) (see Fig. 2C, Table 2).
Scaffold Discontinuity OCT may detect scaffold discontinuity during the process of resorption. The assessment of scaffold discontinuity is the same as that of scaffold fracture after short-term BRS implantation, that is, discontinuity is present if 2 struts overhang each other in the same angular sector of the lumen perimeter, with or without malapposition, or if isolated struts are located near the center of the vessel lumen without obvious connection with other surrounding struts in the 2-dimensional image. Three-dimensional OCT reconstruction is helpful to better understand scaffold discontinuity (see Fig. 3B).
SERIAL OPTICAL COHERENCE TOMOGRAPHIC OBSERVATIONS IN SCAFFOLDED SEGMENTS The OCT results of Absorb BVS Cohorts B1 and B2 have been reported up to 3-year follow-up. The findings of these OCT analyses are illustrated in Fig. 6. There was an initial decrease
Eccentricity As the scaffold degrades, its biomechanical properties are altered, and therefore, eccentricity may change with time and should be assessed for new BRSs. In a small series of 8 patients with 5-year follow-up after Absorb BVS implantation, eccentricity decreased with time (see Fig. 5, Table 2).12 Strut Coverage and Neointimal Hyperplasia The analysis of strut coverage is complex, as it must take into account the embedding and thickening of the frame borders, along with a reduction of the strut central core. The strut area is defined only by its black core, because the light-scattering frame is no longer distinguishable from the surrounding tissue and the tissue begins to fill the strut area, a phenomenon that can be identified by irregular, high-intensity areas. At follow-up, the luminal area follows the endoluminal contour of the neointima between and on top of the apposed struts; this can be traced by semiautomatic detection. In the case of malapposed struts, the endoluminal contour of the vessel wall behind the malapposed struts should be used to define the luminal border. The abluminal side of the central black core is used to delimit the scaffold area. If all struts are apposed, neointimal hyperplasia area is calculated as the difference between the scaffold area and the sum of the lumen and black box areas (ie, scaffold area [lumen area 1 black box area]). In the setting of malapposed struts, neointimal hyperplasia area is calculated by subtracting the sum of the lumen and strut areas from the sum of the scaffold area, ISA area, and the area of malapposed struts and
Fig. 6. Optical coherence tomography (OCT) findings in ABSORB Cohort B trial. OCT was performed postprocedure, at 6, 12, 24, and 36 months. The different parameters are color coded. , Scaffold area in cohort B1; , scaffold area in cohort B2; , mean lumen area in cohort B1; , mean lumen area in cohort B2; , minimum scaffold area in cohort B1; , Minimum scaffold area in cohort B2; , minimum lumen area in cohort B1; , minimum lumen area in cohort B2; , neointimal area in cohort B1; , neointimal area in cohort B2. (Adapted from Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84.)
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in the minimal and mean lumen area that stabilized over the longer term. Although there was an increase in neointima between 1 and 3 years, it was compensated by the parallel increase in the mean and minimum scaffold area, thereby maintaining the lumen area unchanged. A total of 98% percent of struts were covered, and 3 of the 13 scaffolds had malapposed struts with an average malapposition area of 0.60 mm2.13 Serial OCT evaluation of edge and scaffold vascular responses of the Absorb BVS showed less lumen loss at the edges than lumen loss within the scaffold.8 Neointimal coverage of the Absorb BVS seems to be driven by shear stress patterns of the blood flow (Fig. 7). Serial OCT examinations have demonstrated that Absorb BVS may potentially passivate vulnerable plaques (Fig. 8).14 In one such study, 46 patients treated with Absorb BVS and 20 patients treated with bare metal stents (Svelte coronary Integrated Delivery System, a balloonexpandable, cobalt-chromium, thin-strut fixed wire stent) had thin-capped fibroatheromas (TCFAs) identified within the device implantation regions and in the adjacent native coronary segments. At 6- to 12-month follow-up, only 8% of
=
the TCFAs detected at baseline were still present within the Absorb BVS compared with 27% within the bare metal stent implantation segments (P 5 .231). A total of 60% of the TCFAs in native segments did not change their phenotype at follow-up. The more aggressive neointimal response to the bare metal stent resulted in a greater reduction in luminal dimensions compared with the Absorb BVS. The loss of the scaffold’s structural integrity allowed the device to expand and accommodate the tissue that developed and recapped the underlying high-risk plaques.14 The serial changes in atherosclerotic plaques after BRS implantation can be quantified by OCT. In ex vivo validation studies, highly attenuating regions (attenuation coefficient mt 8 mm1) seen on OCT have been associated with the presence of necrotic core or macrophages. Conversely, attenuation coefficient less than 6 mm1 was associated with healthy vessels, calcified plaque, or intimal thickening.15,16 In a small series of 8 patients with 5-year follow-up after Absorb BVS implantation, OCT demonstrated a low-attenuating layer covering the treated atherosclerotic plaques (Fig. 9). In 1 patient, a TCFA was observed at
Fig. 7. (A–C) Distribution of the endothelial shear stress (ESS) and neointimal thickness (NT) in a scaffolded segment. The dashed lines in the reconstructed segment in (A) and (B) indicate the location of the optical coherence tomographic images in 1 and 2. 100 and 200 show the ESS distribution across the circumference of the vessel wall; the neointimal thickness is portrayed in a semitransparent manner. As shown in i, ii, and iii, the ESS is low in the between-strut areas and high on top of the struts. The neointimal tissue appears to be increased in segments with low ESS and reduced in segments with high ESS values. The blood flow streamlines are shown with velocity color coding (right), whereas the ESS distribution along the baseline luminal surface is portrayed according to the colorcoded map (left). The neointimal thickness at 1-year follow-up is shown in a semitransparent fashion. Low ESS and recirculation zones are noted in the interstrut areas, whereas ESS values are high on top of the struts. The ESS distribution seems to affect neointimal formation, because there is increased neointimal tissue in the regions between the struts and minimal neointimal tissue over the struts. (D) Three-dimensional reconstruction of coronary anatomy from the baseline coronary angiographic and OCT data and blood flow simulation, with the local ESS being portrayed in a color-coded map (blue indicates low ESS and red, high ESS). The distribution of the ESS in the scaffolded segment is illustrated at the top right side of the panel, whereas below there is an electron microscopic image acquired 14 days after Absorb BVS implantation in an animal model showing the rugged luminal surface. (D1, D2) Baseline ESS distribution around the circumference of the vessel wall in 2 OCT cross-sectional images. Normal to high ESS noted over a fibroatheroma with a cap thickness of 90 mm in D1, whereas in D2, the ESS is low over the vessel wall and normal over the struts. The asterisk in both images indicates a side branch. At follow-up, the ESS values are normalized in the scaffolded segment and seem to be increased when compared with baseline (E). The magnified view demonstrates the thin layer of neointima that has developed and is portrayed with light gray. High ESS was noted over the fibroatheroma detected at baseline, but the neointimal tissue has sealed the plaque (E1). The low ESS estimated at baseline across the circumference of the vessel wall in D2 is normalized at follow-up (E2). ([A–C] Adapted from Bourantas CV, Papafaklis MI, Kotsia A, et al. Effect of the endothelial shear stress patterns on neointimal proliferation following drug-eluting bioresorbable vascular scaffold implantation: an optical coherence tomography study. JACC Cardiovasc Interv 2014;7:315–24; and [D, E] From Bourantas CV, Papafaklis MI, Garcia-Garcia HM, et al. Short- and long-term implications of a bioresorbable vascular scaffold implantation on the local endothelial shear stress patterns. JACC Cardiovasc Interv 2014;7:100–1.)
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Fig. 8. (A) OCT images acquired from a matched site at baseline, 6 months, and 5 years after Absorb BVS implantation. The amount of tissue overlying the calcific deposition increased from baseline to 6 months because of neointimal response to scaffold implantation. At 5 years, the scaffold struts and neointima have merged into a thick layer of tissue covering the underlying plaque. Arrowheads indicate scaffold struts. GW indicates guidewire artifact. (B) Histologic findings 10 years after Igaki-Tamai bioresorbable scaffold implantation at the left anterior descending coronary artery. The spaces previously occupied by PLLA scaffold struts disappeared. Elastica van Gieson staining shows thick intima. This thick intima consisted of smooth muscle cells and fibrotic tissues without almost no inflammatory cells. ([A] Adapted from Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56.)
the distal scaffold segment with cap disruption and small thrombus.16 Qualitatively, comparison with prior follow-up OCT examinations did not demonstrate any evidence for the accumulation of de novo adluminal necrotic core within the scaffolded segments.16 Conversely, patients treated with metallic DESs seemed to develop neoatherosclerosis within the neointima (see Fig. 9).16 Given the small sample size, and the observation of a different tissue response in 1 patient, these findings require confirmation in larger studies.
OPTICAL COHERENCE TOMOGRAPHY AND SCAFFOLD DEGRADATION OCT may not be sensitive enough to assess the extent of polymer degradation. The absence of strut footprints on OCT was at first interpreted as a sign of complete bioresorption; however, it was subsequently shown that OCT cannot differentiate the polylactide of the polymer from the provisional matrix of proteoglycan formed by connective tissue.13,17 Thus, polymer may no longer be present in the black core areas
OCT for Bioresorbable Scaffolds Assessment
Fig. 9. (A) Example of attenuation analysis. Tissue attenuation properties within adluminal and abluminal contour are measured in all frames and displayed on a color scale (blue represents low-attenuation regions, whereas red and yellow represent high-attenuation regions). For intimal thickness less than 200 mm, as in the 6-o’clock to 7-o’clock position, analysis is not performed because of lack of a sufficient imaging window. (B, C) Spread-out maps demonstrating attenuation coefficient in predefined depths from the vessel surface (100, 200, and 400 mm). In (B) there is a low-attenuating layer of 200 mm separating the underlying plaque (starting at w400 mm) from the lumen. In (C), this layer was absent, and attenuating areas were close to the lumen. (D) Potential paradigm shift in the treatment of atherosclerosis with Absorb BVS. After metal stent implantation, struts are preserved and the neointimal area clearly delineated between stent and lumen contour even at long-term follow-up. There is a possible development of neoatherosclerosis within the neointima. Conversely, bioresorbable scaffolds in longterm follow-up of the neointimal boundaries are unclear after degradation (dotted line), and the intima resembles native plaque, defined as neoplaque. The signal-rich layer is the layer that separates the underlying plaque components from the lumen. (Adapted from Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimuseluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56.)
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Fig. 10. Comparison of serial OCT and histologic findings in a porcine model. OCT cross sections were matched according to the presence of distal metallic markers (red asterisks) at 1 and 3 years. One of the matched struts next to the marker (asterisk) was analyzed by light reflectivity.21 At 3 years, the strut core that was initially black became partially filled by a nucleus exhibiting high light reflectivity. Tracings at the bottom showed graphically the light reflectivity along the scan line of incident light (red). The vertical green dotted lines correspond to the adluminal and abluminal boundaries of the black core either empty or partially occupied by white nucleus. Histologic picture (Movat staining) of porcine coronary artery 36 months after implantation of Absorb scaffold showed provisional matrix (glycoconjugates) in purple, filling the void previously occupied by the polymeric strut. A cellularized (black dots) area with connective tissue (green staining) is located at the center of the strut void and is connected to the subintima. Multilayers of smooth muscle cells are overlying the strut voids. OCT images of the histologic structures in a porcine model are similar to those observed in human. (Adapted from Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84.)
seen on OCT. OCT does provide information regarding scaffold integration, that is, when the scaffold struts start to have cellular areas with connective tissue (Fig. 10).13,17
OVERLAPPING SEGMENTS, BIFURCATIONS, AND 2-DIMENSIONAL VERSUS 3-DIMENSIONAL OPTICAL COHERENCE TOMOGRAPHY Three-dimensional OCT provides much more useful information at bifurcations and
overlapping segments than does 2-dimensional OCT. In overlapping regions, 2-dimensional OCT helps to identify single or stacked struts (inner vs outer) and stacked strut clusters (Fig. 11). Lumen area should be calculated similarly to nonoverlapping segments. Scaffold area at overlapping segments should be calculated by planimetry from the backside (ie, abluminal side) of the black core area of the outermost strut or stacked strut cluster (at the point of all the struts apposing the vessel endothelium) apposing the vessel wall. Where there does not
OCT for Bioresorbable Scaffolds Assessment
Fig. 11. In the cross-sectional images of optical coherence tomography, the metallic markers can be identified as high-echogenic and high–light intensity structures accompanied with backward shadows (asterisks). The 3-dimensional OCT reconstruction helps to understand the overlapping region. (From Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
appear to be any apposition of a single strut or stacked strut cluster to the vessel endothelium, the contour of the scaffold area continues to follow the outermost (most abluminal) scaffold strut or stacked strut cluster. Threedimensional OCT of overlapping regions helps define the type of overlapping, interdigitating struts versus complete overlap.18 Within bifurcations, 3-dimensional OCT enables a detailed assessment of both the longitudinal and cross-sectional relationship between the jailed side branch orifice and the overhanging struts.19 Modifications of the shape of the struts after side branch dilatation can be observed with 3-dimensional OCT. Serial 3-dimensional OCT provides information regarding the evolution of the bifurcation anatomy after scaffold implantation, such as the presence of neointimal bridges, which usually appear as an extension of the preexisting
carina. From a quantitative point of view, 3-dimensional OCT reconstruction can be used to assess the changes over time in the number of compartments and their geometric areas (Fig. 12).
AGREEMENT AND REPRODUCIBILITY OF OPTICAL COHERENCE TOMOGRAPHY FOR THE ASSESSMENT OF BIORESORBABLE SCAFFOLDS OCT has excellent reproducibility for the assessment of incomplete malapposition and struts at side branches.20 OCT is the most accurate technique for measuring scaffold length. There is a moderate agreement with IVUS in the measurement of in-scaffold minimum lumen area assessment at the same coronary segment, and therefore their values should not be used interchangeably.5
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Fig. 12. Three-dimensional OCT side branch classification. (A) Classification based on the relative location with the side-branch ostium. Four different types could be identified: proximal, distal, proximal and distal, or crossing. Dotted lines indicate side-branch ostia; arrowheads indicate tissue bridge. (B) Upper panel shows the bioresorbable vascular scaffold (BVS) with polymeric struts. Yellow circles represent the orifice of the side branch (SB). A nonjailed SB is defined as the complete absence of struts across the orifice (1a) or BVS struts located over the orifice without compartmentalization (1b). Lower panel shows jailed SB orifices are separated into various compartments. Types of SB jailing are expressed in alphabetical letters given according to resemblance of the strut structure across the orifice. ([A] From Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the longterm vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56; and [B] Adapted from Okamura T, Onuma Y, Garcia-Garcia HM, et al. 3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification. JACC Cardiovasc Interv 2010;3:836–44.)
OCT for Bioresorbable Scaffolds Assessment
SUMMARY OCT is a valuable tool for BRS assessment because of its high resolution. It provides detailed and reproducible information regarding the interaction between the device and lumen surface. A dedicated methodology for OCT analysis, different from that for metallic stents, is required for the short- and long-term assessment of BRS.
12.
13.
REFERENCES 1. Serruys PW, Garcia-Garcia HM, Onuma Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur Heart J 2012;33:16–25b. 2. Waksman R. Biodegradable stents: they do their job and disappear. J Invasive Cardiol 2006;18:70–4. 3. Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48. 4. Campos CM, Lemos PA. Bioresorbable vascular scaffolds: novel devices, novel interpretations, and novel interventions strategies. Catheter Cardiovasc Interv 2014;84:46–7. 5. Gutierrez-Chico JL, Serruys PW, Girasis C, et al. Quantitative multi-modality imaging analysis of a fully bioresorbable stent: a head-to-head comparison between QCA, IVUS and OCT. Int J Cardiovasc Imaging 2012;28:467–78. 6. Gutierrez H, Arnold R, Gimeno F, et al. Optical coherence tomography. Initial experience in patients undergoing percutaneous coronary intervention. Rev Esp Cardiol 2008;61:976–9. 7. Radu MD, Raber L, Heo J, et al. Natural history of optical coherence tomography-detected non-flowlimiting edge dissections following drug-eluting stent implantation. EuroIntervention 2014;9:1085–94. 8. Zhang YJ, Iqbal J, Nakatani S, et al, ABSORB Cohort B Study Investigators. Scaffold and edge vascular response following implantation of everolimus-eluting bioresorbable vascular scaffold: a 3 year serial optical coherence tomography study. JACC Cardiovasc Interv 2014;7(12):1361–9. 9. de Jaegere P, Mudra H, Figulla H, et al. Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study). Eur Heart J 1998;19:1214–23. 10. Otake H, Shite J, Ako J, et al. Local determinants of thrombus formation following sirolimus-eluting stent implantation assessed by optical coherence tomography. JACC Cardiovasc Interv 2009;2:459–66. 11. Mattesini A, Secco GG, Dall’Ara G, et al. ABSORB biodegradable stents versus second-generation
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metal stents: a comparison study of 100 complex lesions treated under OCT guidance. JACC Cardiovasc Interv 2014;7:741–50. Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56. Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84. Bourantas CV, Serruys PW, Nakatani S, et al. Bioresorbable vascular scaffold treatment induces the formation of neointimal cap that seals the underlying plaque without compromising the luminal dimensions: a concept based on serial optical coherence tomography data. EuroIntervention 2014. [Epub ahead of print]. van Soest G, Goderie T, Regar E, et al. Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging. J Biomed Opt 2010;15:011105. Ughi GJ, Adriaenssens T, Sinnaeve P, et al. Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images. Biomed Opt Express 2013;4:1014–30. Onuma Y, Serruys PW, Perkins LE, et al. Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: an attempt to decipher the human optical coherence tomography images in the ABSORB trial. Circulation 2010;122:2288–300. Farooq V, Onuma Y, Radu M, et al. Optical coherence tomography (OCT) of overlapping bioresorbable scaffolds: from benchwork to clinical application. EuroIntervention 2011;7:386–99. Okamura T, Onuma Y, Garcia-Garcia HM, et al. 3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification. JACC Cardiovasc Interv 2010;3:836–44. Gomez-Lara J, Brugaletta S, Diletti R, et al. Agreement and reproducibility of gray-scale intravascular ultrasound and optical coherence tomography for the analysis of the bioresorbable vascular scaffold. Catheter Cardiovasc Interv 2012;79:890–902. Nakatani S, Onuma Y, Ishibashi Y, et al. Temporal evolution of strut light intensity after implantation of bioresorbable polymeric intracoronary scaffolds in the ABSORB Cohort B trial - an application of a new quantitative method based on optical coherence tomography. Circ J 2014;78:1873–81.
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KEY POINTS The analysis of bioresorbable scaffolds (BRSs) by optical coherence tomography (OCT) requires a dedicated methodology, as the polymeric scaffold has a distinct appearance and undergoes dynamic structural changes with time, unlike metallic stents. The high resolution of OCT allows for the detailed assessment of scaffold implantation, rupture, discontinuity, and strut integration. OCT does not provide reliable information on the extent of scaffold degradation, as it cannot differentiate between polylactide polymer and the provisional matrix of proteoglycan formed by connective tissue. Three-dimensional OCT reconstruction can aid in the evaluation of BRS in special scenarios such as overlapping scaffold segments and bifurcations.
INTRODUCTION BRSs represent a novel approach in the treatment of coronary artery disease. They support the vessel transiently to maintain patency after intervention, deliver antiproliferative drug to the vessel wall, and then gradually degrade.1,2 BRS technology has matured, and there are numerous devices that are commercially available outside the United States or are undergoing preclinical or clinical evaluation (Fig. 1). BRS has required new imaging modalities, methodologies, and strategies, because
scaffold design, degradation rate, loss of mechanical properties (Table 1), coating, and drug deliverability may affect BRS safety and efficacy.3,4 OCT has played a central role in understanding the short and long term BRS performance, OCT provides more detailed and precise morphologic information about BRS than does intravascular ultrasonography (IVUS) because of its higher resolution.5,6 This review summarizes the methodology and clinical application of OCT in the assessment of BRS, in particular for the commercially available Absorb Bioresorbable
The authors have nothing to disclose. a Department of Interventional Cardiology, Thoraxcenter, Erasmus University Medical Centre, Dr. Molewaterplein 40, Rotterdam 3015 GD, The Netherlands; b Department of Interventional Cardiology Heart Institute (InCor), University of Sa˜o Paulo Medical School, Avenida Doutor Ene´as de Carvalho Aguiar, 44 - Terceiro Andar, Sao Paulo 05403-900, Brazil; c International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; d Medical Affairs, Cardialysis, Westblaak 98, Entrance B, Rotterdam 3012 KM, The Netherlands * Corresponding author. Westblaak 98, Entrance B, Rotterdam 3012 KM, The Netherlands. E-mail address: [email protected] Intervent Cardiol Clin 4 (2015) 333–349 http://dx.doi.org/10.1016/j.iccl.2015.03.001 2211-7458/15/$ – see front matter ª 2015 Elsevier Inc. All rights reserved.
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Fig. 1. Optical coherence tomography images of different bioresorbable vascular scaffolds. Absorb BVS 1.1 (Abbott Vascular, Santa Clara, CA, USA); Fortitude (Amaranth Medical, Mountain View, CA, USA); DESolve BRS (Elixir, Sunnyvale, CA, USA); DREAMS 1.0 absorbable metallic scaffold (Biotronik, Berlin, Germany); Ideal II BioStent (Xenogenics, Philadelphia, PA, USA); Igaki-Tamai scaffold (Kyoto Medical Planning Co, Kyoto, Japan); On-AVS (Orbus Neich, Wanchai, Hong Kong); REVA (REVA Medical Inc, San Diego, CA, USA). An OCT image for IgakiTamai was not available at baseline.
Table 1 Mechanical properties and degradation rate of different material candidates for bioresorbable coronary scaffolds
a
Material
Tensile Strength (MPa)
Elongation (%)
Degradation Time
Poly(L-lactide)
60–70
2–6
24 moa
Poly(DL-lactide)
45–55
2–6
12–16 moa
Poly(glycolide)
90–110
1–2
6–12 moa
50/50
40–50
1–4
1–2 moa
82/18 L-lactide/glycolide
60–70
2–6
12–18 moa
70/30 L-lactide/ε-aprolactone
18–22
>100
12–24 moa
DL-lactide/glycolide
Pure Fe
200
40
0.19 mm/y
Fe-35 Mn alloy
430
30
0.44 mm/y
WE43 alloy
280
2
1.35 mm/y
Degradation time depends on geometry. Data from Moravej M, Mantovani D. Biodegradable metals for cardiovascular stent application: interests and new opportunities. Int J Mol Sci 2011;12:4250–70; and van Alst M, Eenink MJ, Kruft MA, et al. ABC’s of bioabsorption: application of lactide based polymers in fully resorbable cardiovascular stents. EuroIntervention 2009;5(Suppl F):F23–7.
OCT for Bioresorbable Scaffolds Assessment
Vascular Scaffold (BVS) (Abbot Vascular, Santa Clara, CA, USA), as this device had the most extensive short- and long-term follow-up data.
RATIONALE FOR THE NEED FOR A DEDICATED ANALYSIS METHODOLOGY FOR THE OPTICAL COHERENCE TOMOGRAPHIC ASSESSMENT OF BIORESORBABLE SCAFFOLDS The OCT appearance of polymeric scaffolds differs significantly from that of metallic scaffolds and stents (Fig. 2A). The appearance of magnesium scaffolds immediately after implantation is similar to that of a permanent metallic stent, that is, a bright strut with well-delimited borders with a shadow behind (see Fig. 2A). In contradistinction, polymeric struts are optically translucent and appear as a black central core framed by light-scattering borders that do not shadow the vessel wall, and therefore the complete thickness of the scaffold strut can be visualized (see Fig. 2B). The main quantitative measurements for scaffold evaluation by OCT include strut core area, strut area, lumen area, scaffold area, incomplete strut apposition (ISA) area, and neointimal area. Because polymeric scaffolds scatter light differently and have different OCT characteristics than metallic stents/scaffolds (see Fig. 2B, C), these measurements must be acquired using different image analysis rules.
OPTICAL COHERENCE TOMOGRAPHIC EVALUATION OF BIORESORBABLE SCAFFOLDS AT TIME OF IMPLANTATION Several OCT parameters can be collected at the time of short-term implantation of the BRS; these are summarized in Table 2. Key quantifications include the lumen and scaffold areas, the magnitude of ISA, lumen prolapse, and flow area. The high resolution provided by OCT also allows the operator to visualize the quality of scaffold implantation and the potential complications related to it. Important analyses include assessments of short-term strut fracture, edge dissection, eccentricity, and symmetry.
Contours At baseline, the lumen and scaffold contours are obtained with a semiautomated detection algorithm available in numerous off-line software packages. These contours can be corrected manually if necessary. Lumen and Scaffold Areas Because the polymeric struts are translucent, the vessel lumen border can be visualized and the
vessel lumen area delineated along the external (abluminal) side of the struts. The scaffold area is measured by joining the internal middle points of the abluminal side of the black cores of the apposed struts or the abluminal edge of the frame borders of malapposed struts. In the absence of ISA and plaque prolapse, the scaffold area is identical to the lumen area (see Fig. 2C).
Incomplete Strut Apposition ISA is defined by a clear separation between the abluminal side of the strut and the vessel wall. ISA area is delineated by the abluminal side of the frame border of the malapposed struts and the endoluminal contour of the lumen. Lumen Prolapse Several different parameters can be collected in the case of lumen or plaque prolapse protruding between the struts into the lumen. The prolapse area can be estimated by the planimetered difference between the prolapsed contour (ie, lumen contour) and the scaffold area. An intraluminal defect that is separated from the vessel wall (eg, thrombus) can also be quantified as an area. Flow Area Flow area takes into account ISA, plaque prolapse, and intraluminal defects. It is defined as the difference between the sum of the scaffold and ISA areas and the sum of the areas of intraluminal struts, prolapse, and intraluminal defect (ie, flow area 5 [scaffold area 1 ISA area] [intraluminal strut areas 1 prolapse area 1 intraluminal defect area]). Short-term Strut Fracture The diagnosis of short-term strut fracture due to balloon overdilation can be established if 2 struts overhang each other within the same angular sector of the lumen perimeter (Fig. 3). This complication may be observed with or without concomitant strut malapposition. However, if isolated struts are located more or less at the center of the vessel without an obvious connection with other surrounding struts, strut fracture may also be present. It is helpful to perform 3-dimensional reconstruction of the OCT dataset to confirm the diagnosis. Edge Dissection Edge dissection is defined by OCT as the disruption of the endoluminal vessel surface at the proximal and distal edges of the BRS (Fig. 4).7 In the ABSORB Cohort B trial, 24% of patients had proximal and 42% had distal edge dissection flaps postprocedure.8 On follow-up, proximal and distal edge dissection flaps seem to
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Fig. 2. (A) Representative optical coherence tomographic image of the drug-eluting absorbable metal scaffold DREAMS (Biotronik, Bu¨lach, Switzerland) immediately after implantation looks like a permanent metallic stent (left). Absorb BVS has optically translucent struts and appears as a black central core framed by light-scattering borders that do not shadow the vessel wall and allow complete imaging of the strut thickness (right). (B) Methodology for the assessment of incomplete scaffold apposition (ISA) with the drug-eluting absorbable metal scaffold DREAMS. (C) Newly implanted bioresorbable scaffold. Differences in the methodology of OCT assessment between metallic stents and BVS are illustrated. Panel 1. Metallic stent approach. Note that with metallic scaffold/stent analysis, device area is calculated by planimetry of the endoluminal border of the struts. Lumen area, 10.16 mm2; stent area, 7.84 mm2, ISA, 2.32 mm2. Panel 2. BVS approach. Lumen area, 10.16 mm2; stent area, 9.58 mm2; ISA, 0.58 mm2. Panel 3. Additional BVS analyses. Strut area, 0.61 mm2; blood flow area (lumen area strut area), 9.55 mm2. Panel 4. Follow-up OCT imaging of BVS. Strut area is defined only by its black core, because the light-scattering frame is no longer distinguishable from the surrounding tissue. Neointimal area is defined by (scaffold area lumen area strut area). ([C] Adapted from Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
OCT for Bioresorbable Scaffolds Assessment
Table 2 Definitions and formulas for the quantification of OCT parameters for the assessment of BRSs Parameter
Formula
Definition and Notes
Eccentricity index
Minimum scaffold diameter/maximum scaffold diameter in a frame
The average of all eccentricity indices of each frame within scaffolded segment is calculated
Symmetry index
(Minimum scaffold diameter maximum scaffold diameter)/ maximum scaffold diameter within a scaffolded segment
The maximum and the minimum stent/scaffold diameters in this calculation were possibly located in 2 different frames along the length of the device implanted
Scaffold area
At baseline, the scaffold area is measured by joining the middle points of the abluminal sides of the black cores of the apposed struts or the abluminal edge of the frame borders of malapposed struts. At follow-up, the abluminal side of the central black core is used to delimit the scaffold area
Blood flow area
(Scaffold area 1 ISA area) (intraluminal strut areas 1 prolapse area 1 intraluminal defect area)
Neointimal hyperplasia area
i. In case of all struts apposed Scaffold area [lumen area 1 black box area] ii. In case of malapposed struts [Scaffold area 1 ISA area 1 malapposed strut with surrounding tissues] [lumen area 1 strut area]
Note the difference of methodology with that of gray-scale IVUS
Thickness of tissue coverage
Distance between the abluminal site of the strut and the lumen strut thickness
Since the strut thickness is 150 mm (ABSORB), the strut was considered as covered whenever the thickness of the coverage was more than this threshold value. This method may slightly underestimate the thickness of the coverage because it does not take into account changes in the size of the strut core over time
Adapted from Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.
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Fig. 3. Representative OCT image of scaffold fracture and discontinuity. (A) Scaffold fracture. During the index procedure after postdilatation of an Absorb BVS, OCT cross-sectional image shows scaffold fracture (blue arrow, left). The strut luminal and abluminal surfaces are no longer orientated perpendicular to the light source. OCT crosssectional image 1 month later shows extensive strut disarray (dotted blue arrow, right). (B) Scaffold discontinuity. OCT acquisition 6 months after Absorb BVS implantation. In the 2-dimensional (cross-sectional) OCT image, extreme malapposition of 1 strut is seen (panel B2, yellow arrow). In the 3-dimensional reconstruction, the overhanging strut is clearly identified in its whole trajectory (panel B3, B4; yellow arrow). Further intervention was deferred because of lack of ischemic symptoms. ([A] Adapted from Ormiston JA, De Vroey F, Serruys PW, et al. Bioresorbable polymeric vascular scaffolds: a cautionary tale. Circ Cardiovasc Interv 2011;4:535– 8; and [B] From Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
have resolved. In serial OCT analysis of BRSs, postprocedural proximal edge dissection was noted in 21% of cases and distal edge dissection in 38% of cases, compared with 2% and 5% at 6 months, respectively. At 1 year, an edge dissection was present in only 2% (proximal) and none were observed at 2- and 3-year follow-up. No scaffold thrombosis was reported in this trial.8 Therefore, although edge dissection by OCT is often detected, most of these dissections healed within 6 months without any clinical
sequelae. However, the small sample size of this study limits any definitive conclusion with respect to the effect of residual edge dissection on clinical outcomes.
Eccentricity and Symmetry The eccentricity and symmetry of implanted BRSs are easily assessed by OCT (see Table 2). These parameters have been shown to be associated with clinical outcomes after metallic stents.9,10 With the clinical adoption of various
OCT for Bioresorbable Scaffolds Assessment
Fig. 4. Representative imaging of a dissection at the distal edge of Absorb BVS. (A) Longitudinal view of a distal dissection. (B) Three-dimensional reconstruction of OCT pullback showing luminal disruption at distal edge of the scaffold (double white arrow). (C, D) Three-dimensional reconstruction at 6-month and 2-year follow-up, respectively, demonstrating that the dissection has healed. (E) No distal edge dissection is visible from the angiograms postprocedure (yellow arrow). (F) OCT cross-sectional images immediately after implantation show that a dissection extends into the media. (G) OCT image at 6-month follow-up demonstrates an increase in lumen area at that region without visible dissection. (H) At 2-year follow-up, the lumen area has decreased with detected calcific tissue. Asterisk, side branch. (From Zhang YJ, Iqbal J, Nakatani S, et al. ABSORB Cohort B Study Investigators. Scaffold and edge vascular response following implantation of everolimus-eluting bioresorbable vascular scaffold: a 3 year serial optical coherence tomography study. JACC Cardiovasc Interv 2014;7(12):1361–9.)
bioresorbable devices, the reevaluation of the clinical effect of these geometric parameters is required at short- and long-term follow-up. The eccentricity ratio is defined as the ratio of the minimum and maximum diameters of the scaffold in each frame. The eccentricity index is obtained by calculating the average of all eccentricity ratios along the length of the scaffold.3 The symmetry index is derived from the maximum scaffold diameter and minimum scaffold diameter along the length of the BRS, which may be located within different frames. It is calculated as the difference between the maximum scaffold diameter and the minimum scaffold diameter, divided by the maximum scaffold diameter.3 It must be emphasized that the maximum and the minimum scaffold diameters
in this calculation may be located in 2 different frames along the length of the implanted device (Fig. 5).
Bioresorbable Scaffold Versus Drug-Eluting Stent at Time of Implantation BRSs have distinct mechanical properties compared with metallic stents that could influence the aforementioned OCT parameters. Mattesini and colleagues11 compared the final, postimplantation results of the Absorb BVS and second-generation drug-eluting stents (DESs) using OCT. A total of 50 complex coronary lesions (class B2/C by the American College of Cardiology/American Heart Association definition) treated with a BVS undergoing a final OCT examination were compared with an equal
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Fig. 5. Definition of the symmetry and eccentricity indices according to OCT. Minimum and maximum diameters along the length of the device are shown. Two cross-sections with different eccentricity indices are also shown.
number of matched lesions treated with second-generation DESs. In the BRS group, there was more extensive lesion preparation (eg, significantly greater balloon diameter:reference vessel diameter ratio and higher inflation predilation pressure) and significantly higher postdilatation pressure used. Final OCT examination demonstrated a trend toward greater tissue prolapse area (P 5 .08) and a significantly higher rate of proximal edge ISA (P 5 .04) in the BVS group. There was no significant difference in the overall ISA, mean lumen area, and eccentricity index between the 2 groups. There
were 2 cases of strut fractures in the lesions treated with BVS, whereas none was observed with DES.11
OPTICAL COHERENCE TOMOGRAPHIC EVALUATION OF BIORESORBABLE SCAFFOLD OVER LONG-TERM FOLLOW-UP Because BRSs are designed to degrade with time after implantation, the structural characteristics of the scaffold are dynamic and can be well visualized by OCT imaging. Key parameters that may
OCT for Bioresorbable Scaffolds Assessment
be assessed during ongoing follow-up include the presence of any scaffold discontinuity, scaffold eccentricity, strut coverage, and neointimal hyperplasia.
surrounding tissues (ie, [scaffold area 1 ISA area 1 malapposed strut with surrounding tissues] [lumen area 1 strut area]) (see Fig. 2C, Table 2).
Scaffold Discontinuity OCT may detect scaffold discontinuity during the process of resorption. The assessment of scaffold discontinuity is the same as that of scaffold fracture after short-term BRS implantation, that is, discontinuity is present if 2 struts overhang each other in the same angular sector of the lumen perimeter, with or without malapposition, or if isolated struts are located near the center of the vessel lumen without obvious connection with other surrounding struts in the 2-dimensional image. Three-dimensional OCT reconstruction is helpful to better understand scaffold discontinuity (see Fig. 3B).
SERIAL OPTICAL COHERENCE TOMOGRAPHIC OBSERVATIONS IN SCAFFOLDED SEGMENTS The OCT results of Absorb BVS Cohorts B1 and B2 have been reported up to 3-year follow-up. The findings of these OCT analyses are illustrated in Fig. 6. There was an initial decrease
Eccentricity As the scaffold degrades, its biomechanical properties are altered, and therefore, eccentricity may change with time and should be assessed for new BRSs. In a small series of 8 patients with 5-year follow-up after Absorb BVS implantation, eccentricity decreased with time (see Fig. 5, Table 2).12 Strut Coverage and Neointimal Hyperplasia The analysis of strut coverage is complex, as it must take into account the embedding and thickening of the frame borders, along with a reduction of the strut central core. The strut area is defined only by its black core, because the light-scattering frame is no longer distinguishable from the surrounding tissue and the tissue begins to fill the strut area, a phenomenon that can be identified by irregular, high-intensity areas. At follow-up, the luminal area follows the endoluminal contour of the neointima between and on top of the apposed struts; this can be traced by semiautomatic detection. In the case of malapposed struts, the endoluminal contour of the vessel wall behind the malapposed struts should be used to define the luminal border. The abluminal side of the central black core is used to delimit the scaffold area. If all struts are apposed, neointimal hyperplasia area is calculated as the difference between the scaffold area and the sum of the lumen and black box areas (ie, scaffold area [lumen area 1 black box area]). In the setting of malapposed struts, neointimal hyperplasia area is calculated by subtracting the sum of the lumen and strut areas from the sum of the scaffold area, ISA area, and the area of malapposed struts and
Fig. 6. Optical coherence tomography (OCT) findings in ABSORB Cohort B trial. OCT was performed postprocedure, at 6, 12, 24, and 36 months. The different parameters are color coded. , Scaffold area in cohort B1; , scaffold area in cohort B2; , mean lumen area in cohort B1; , mean lumen area in cohort B2; , minimum scaffold area in cohort B1; , Minimum scaffold area in cohort B2; , minimum lumen area in cohort B1; , minimum lumen area in cohort B2; , neointimal area in cohort B1; , neointimal area in cohort B2. (Adapted from Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84.)
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in the minimal and mean lumen area that stabilized over the longer term. Although there was an increase in neointima between 1 and 3 years, it was compensated by the parallel increase in the mean and minimum scaffold area, thereby maintaining the lumen area unchanged. A total of 98% percent of struts were covered, and 3 of the 13 scaffolds had malapposed struts with an average malapposition area of 0.60 mm2.13 Serial OCT evaluation of edge and scaffold vascular responses of the Absorb BVS showed less lumen loss at the edges than lumen loss within the scaffold.8 Neointimal coverage of the Absorb BVS seems to be driven by shear stress patterns of the blood flow (Fig. 7). Serial OCT examinations have demonstrated that Absorb BVS may potentially passivate vulnerable plaques (Fig. 8).14 In one such study, 46 patients treated with Absorb BVS and 20 patients treated with bare metal stents (Svelte coronary Integrated Delivery System, a balloonexpandable, cobalt-chromium, thin-strut fixed wire stent) had thin-capped fibroatheromas (TCFAs) identified within the device implantation regions and in the adjacent native coronary segments. At 6- to 12-month follow-up, only 8% of
=
the TCFAs detected at baseline were still present within the Absorb BVS compared with 27% within the bare metal stent implantation segments (P 5 .231). A total of 60% of the TCFAs in native segments did not change their phenotype at follow-up. The more aggressive neointimal response to the bare metal stent resulted in a greater reduction in luminal dimensions compared with the Absorb BVS. The loss of the scaffold’s structural integrity allowed the device to expand and accommodate the tissue that developed and recapped the underlying high-risk plaques.14 The serial changes in atherosclerotic plaques after BRS implantation can be quantified by OCT. In ex vivo validation studies, highly attenuating regions (attenuation coefficient mt 8 mm1) seen on OCT have been associated with the presence of necrotic core or macrophages. Conversely, attenuation coefficient less than 6 mm1 was associated with healthy vessels, calcified plaque, or intimal thickening.15,16 In a small series of 8 patients with 5-year follow-up after Absorb BVS implantation, OCT demonstrated a low-attenuating layer covering the treated atherosclerotic plaques (Fig. 9). In 1 patient, a TCFA was observed at
Fig. 7. (A–C) Distribution of the endothelial shear stress (ESS) and neointimal thickness (NT) in a scaffolded segment. The dashed lines in the reconstructed segment in (A) and (B) indicate the location of the optical coherence tomographic images in 1 and 2. 100 and 200 show the ESS distribution across the circumference of the vessel wall; the neointimal thickness is portrayed in a semitransparent manner. As shown in i, ii, and iii, the ESS is low in the between-strut areas and high on top of the struts. The neointimal tissue appears to be increased in segments with low ESS and reduced in segments with high ESS values. The blood flow streamlines are shown with velocity color coding (right), whereas the ESS distribution along the baseline luminal surface is portrayed according to the colorcoded map (left). The neointimal thickness at 1-year follow-up is shown in a semitransparent fashion. Low ESS and recirculation zones are noted in the interstrut areas, whereas ESS values are high on top of the struts. The ESS distribution seems to affect neointimal formation, because there is increased neointimal tissue in the regions between the struts and minimal neointimal tissue over the struts. (D) Three-dimensional reconstruction of coronary anatomy from the baseline coronary angiographic and OCT data and blood flow simulation, with the local ESS being portrayed in a color-coded map (blue indicates low ESS and red, high ESS). The distribution of the ESS in the scaffolded segment is illustrated at the top right side of the panel, whereas below there is an electron microscopic image acquired 14 days after Absorb BVS implantation in an animal model showing the rugged luminal surface. (D1, D2) Baseline ESS distribution around the circumference of the vessel wall in 2 OCT cross-sectional images. Normal to high ESS noted over a fibroatheroma with a cap thickness of 90 mm in D1, whereas in D2, the ESS is low over the vessel wall and normal over the struts. The asterisk in both images indicates a side branch. At follow-up, the ESS values are normalized in the scaffolded segment and seem to be increased when compared with baseline (E). The magnified view demonstrates the thin layer of neointima that has developed and is portrayed with light gray. High ESS was noted over the fibroatheroma detected at baseline, but the neointimal tissue has sealed the plaque (E1). The low ESS estimated at baseline across the circumference of the vessel wall in D2 is normalized at follow-up (E2). ([A–C] Adapted from Bourantas CV, Papafaklis MI, Kotsia A, et al. Effect of the endothelial shear stress patterns on neointimal proliferation following drug-eluting bioresorbable vascular scaffold implantation: an optical coherence tomography study. JACC Cardiovasc Interv 2014;7:315–24; and [D, E] From Bourantas CV, Papafaklis MI, Garcia-Garcia HM, et al. Short- and long-term implications of a bioresorbable vascular scaffold implantation on the local endothelial shear stress patterns. JACC Cardiovasc Interv 2014;7:100–1.)
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Fig. 8. (A) OCT images acquired from a matched site at baseline, 6 months, and 5 years after Absorb BVS implantation. The amount of tissue overlying the calcific deposition increased from baseline to 6 months because of neointimal response to scaffold implantation. At 5 years, the scaffold struts and neointima have merged into a thick layer of tissue covering the underlying plaque. Arrowheads indicate scaffold struts. GW indicates guidewire artifact. (B) Histologic findings 10 years after Igaki-Tamai bioresorbable scaffold implantation at the left anterior descending coronary artery. The spaces previously occupied by PLLA scaffold struts disappeared. Elastica van Gieson staining shows thick intima. This thick intima consisted of smooth muscle cells and fibrotic tissues without almost no inflammatory cells. ([A] Adapted from Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56.)
the distal scaffold segment with cap disruption and small thrombus.16 Qualitatively, comparison with prior follow-up OCT examinations did not demonstrate any evidence for the accumulation of de novo adluminal necrotic core within the scaffolded segments.16 Conversely, patients treated with metallic DESs seemed to develop neoatherosclerosis within the neointima (see Fig. 9).16 Given the small sample size, and the observation of a different tissue response in 1 patient, these findings require confirmation in larger studies.
OPTICAL COHERENCE TOMOGRAPHY AND SCAFFOLD DEGRADATION OCT may not be sensitive enough to assess the extent of polymer degradation. The absence of strut footprints on OCT was at first interpreted as a sign of complete bioresorption; however, it was subsequently shown that OCT cannot differentiate the polylactide of the polymer from the provisional matrix of proteoglycan formed by connective tissue.13,17 Thus, polymer may no longer be present in the black core areas
OCT for Bioresorbable Scaffolds Assessment
Fig. 9. (A) Example of attenuation analysis. Tissue attenuation properties within adluminal and abluminal contour are measured in all frames and displayed on a color scale (blue represents low-attenuation regions, whereas red and yellow represent high-attenuation regions). For intimal thickness less than 200 mm, as in the 6-o’clock to 7-o’clock position, analysis is not performed because of lack of a sufficient imaging window. (B, C) Spread-out maps demonstrating attenuation coefficient in predefined depths from the vessel surface (100, 200, and 400 mm). In (B) there is a low-attenuating layer of 200 mm separating the underlying plaque (starting at w400 mm) from the lumen. In (C), this layer was absent, and attenuating areas were close to the lumen. (D) Potential paradigm shift in the treatment of atherosclerosis with Absorb BVS. After metal stent implantation, struts are preserved and the neointimal area clearly delineated between stent and lumen contour even at long-term follow-up. There is a possible development of neoatherosclerosis within the neointima. Conversely, bioresorbable scaffolds in longterm follow-up of the neointimal boundaries are unclear after degradation (dotted line), and the intima resembles native plaque, defined as neoplaque. The signal-rich layer is the layer that separates the underlying plaque components from the lumen. (Adapted from Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimuseluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56.)
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Fig. 10. Comparison of serial OCT and histologic findings in a porcine model. OCT cross sections were matched according to the presence of distal metallic markers (red asterisks) at 1 and 3 years. One of the matched struts next to the marker (asterisk) was analyzed by light reflectivity.21 At 3 years, the strut core that was initially black became partially filled by a nucleus exhibiting high light reflectivity. Tracings at the bottom showed graphically the light reflectivity along the scan line of incident light (red). The vertical green dotted lines correspond to the adluminal and abluminal boundaries of the black core either empty or partially occupied by white nucleus. Histologic picture (Movat staining) of porcine coronary artery 36 months after implantation of Absorb scaffold showed provisional matrix (glycoconjugates) in purple, filling the void previously occupied by the polymeric strut. A cellularized (black dots) area with connective tissue (green staining) is located at the center of the strut void and is connected to the subintima. Multilayers of smooth muscle cells are overlying the strut voids. OCT images of the histologic structures in a porcine model are similar to those observed in human. (Adapted from Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84.)
seen on OCT. OCT does provide information regarding scaffold integration, that is, when the scaffold struts start to have cellular areas with connective tissue (Fig. 10).13,17
OVERLAPPING SEGMENTS, BIFURCATIONS, AND 2-DIMENSIONAL VERSUS 3-DIMENSIONAL OPTICAL COHERENCE TOMOGRAPHY Three-dimensional OCT provides much more useful information at bifurcations and
overlapping segments than does 2-dimensional OCT. In overlapping regions, 2-dimensional OCT helps to identify single or stacked struts (inner vs outer) and stacked strut clusters (Fig. 11). Lumen area should be calculated similarly to nonoverlapping segments. Scaffold area at overlapping segments should be calculated by planimetry from the backside (ie, abluminal side) of the black core area of the outermost strut or stacked strut cluster (at the point of all the struts apposing the vessel endothelium) apposing the vessel wall. Where there does not
OCT for Bioresorbable Scaffolds Assessment
Fig. 11. In the cross-sectional images of optical coherence tomography, the metallic markers can be identified as high-echogenic and high–light intensity structures accompanied with backward shadows (asterisks). The 3-dimensional OCT reconstruction helps to understand the overlapping region. (From Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48.)
appear to be any apposition of a single strut or stacked strut cluster to the vessel endothelium, the contour of the scaffold area continues to follow the outermost (most abluminal) scaffold strut or stacked strut cluster. Threedimensional OCT of overlapping regions helps define the type of overlapping, interdigitating struts versus complete overlap.18 Within bifurcations, 3-dimensional OCT enables a detailed assessment of both the longitudinal and cross-sectional relationship between the jailed side branch orifice and the overhanging struts.19 Modifications of the shape of the struts after side branch dilatation can be observed with 3-dimensional OCT. Serial 3-dimensional OCT provides information regarding the evolution of the bifurcation anatomy after scaffold implantation, such as the presence of neointimal bridges, which usually appear as an extension of the preexisting
carina. From a quantitative point of view, 3-dimensional OCT reconstruction can be used to assess the changes over time in the number of compartments and their geometric areas (Fig. 12).
AGREEMENT AND REPRODUCIBILITY OF OPTICAL COHERENCE TOMOGRAPHY FOR THE ASSESSMENT OF BIORESORBABLE SCAFFOLDS OCT has excellent reproducibility for the assessment of incomplete malapposition and struts at side branches.20 OCT is the most accurate technique for measuring scaffold length. There is a moderate agreement with IVUS in the measurement of in-scaffold minimum lumen area assessment at the same coronary segment, and therefore their values should not be used interchangeably.5
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Fig. 12. Three-dimensional OCT side branch classification. (A) Classification based on the relative location with the side-branch ostium. Four different types could be identified: proximal, distal, proximal and distal, or crossing. Dotted lines indicate side-branch ostia; arrowheads indicate tissue bridge. (B) Upper panel shows the bioresorbable vascular scaffold (BVS) with polymeric struts. Yellow circles represent the orifice of the side branch (SB). A nonjailed SB is defined as the complete absence of struts across the orifice (1a) or BVS struts located over the orifice without compartmentalization (1b). Lower panel shows jailed SB orifices are separated into various compartments. Types of SB jailing are expressed in alphabetical letters given according to resemblance of the strut structure across the orifice. ([A] From Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the longterm vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56; and [B] Adapted from Okamura T, Onuma Y, Garcia-Garcia HM, et al. 3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification. JACC Cardiovasc Interv 2010;3:836–44.)
OCT for Bioresorbable Scaffolds Assessment
SUMMARY OCT is a valuable tool for BRS assessment because of its high resolution. It provides detailed and reproducible information regarding the interaction between the device and lumen surface. A dedicated methodology for OCT analysis, different from that for metallic stents, is required for the short- and long-term assessment of BRS.
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REFERENCES 1. Serruys PW, Garcia-Garcia HM, Onuma Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur Heart J 2012;33:16–25b. 2. Waksman R. Biodegradable stents: they do their job and disappear. J Invasive Cardiol 2006;18:70–4. 3. Garcia-Garcia HM, Serruys PW, Campos CM, et al. Assessing bioresorbable coronary devices: methods and parameters. JACC Cardiovasc Imaging 2014;7:1130–48. 4. Campos CM, Lemos PA. Bioresorbable vascular scaffolds: novel devices, novel interpretations, and novel interventions strategies. Catheter Cardiovasc Interv 2014;84:46–7. 5. Gutierrez-Chico JL, Serruys PW, Girasis C, et al. Quantitative multi-modality imaging analysis of a fully bioresorbable stent: a head-to-head comparison between QCA, IVUS and OCT. Int J Cardiovasc Imaging 2012;28:467–78. 6. Gutierrez H, Arnold R, Gimeno F, et al. Optical coherence tomography. Initial experience in patients undergoing percutaneous coronary intervention. Rev Esp Cardiol 2008;61:976–9. 7. Radu MD, Raber L, Heo J, et al. Natural history of optical coherence tomography-detected non-flowlimiting edge dissections following drug-eluting stent implantation. EuroIntervention 2014;9:1085–94. 8. Zhang YJ, Iqbal J, Nakatani S, et al, ABSORB Cohort B Study Investigators. Scaffold and edge vascular response following implantation of everolimus-eluting bioresorbable vascular scaffold: a 3 year serial optical coherence tomography study. JACC Cardiovasc Interv 2014;7(12):1361–9. 9. de Jaegere P, Mudra H, Figulla H, et al. Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study). Eur Heart J 1998;19:1214–23. 10. Otake H, Shite J, Ako J, et al. Local determinants of thrombus formation following sirolimus-eluting stent implantation assessed by optical coherence tomography. JACC Cardiovasc Interv 2009;2:459–66. 11. Mattesini A, Secco GG, Dall’Ara G, et al. ABSORB biodegradable stents versus second-generation
14.
15.
16.
17.
18.
19.
20.
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metal stents: a comparison study of 100 complex lesions treated under OCT guidance. JACC Cardiovasc Interv 2014;7:741–50. Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol 2014;64(22):2343–56. Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84. Bourantas CV, Serruys PW, Nakatani S, et al. Bioresorbable vascular scaffold treatment induces the formation of neointimal cap that seals the underlying plaque without compromising the luminal dimensions: a concept based on serial optical coherence tomography data. EuroIntervention 2014. [Epub ahead of print]. van Soest G, Goderie T, Regar E, et al. Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging. J Biomed Opt 2010;15:011105. Ughi GJ, Adriaenssens T, Sinnaeve P, et al. Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images. Biomed Opt Express 2013;4:1014–30. Onuma Y, Serruys PW, Perkins LE, et al. Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: an attempt to decipher the human optical coherence tomography images in the ABSORB trial. Circulation 2010;122:2288–300. Farooq V, Onuma Y, Radu M, et al. Optical coherence tomography (OCT) of overlapping bioresorbable scaffolds: from benchwork to clinical application. EuroIntervention 2011;7:386–99. Okamura T, Onuma Y, Garcia-Garcia HM, et al. 3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification. JACC Cardiovasc Interv 2010;3:836–44. Gomez-Lara J, Brugaletta S, Diletti R, et al. Agreement and reproducibility of gray-scale intravascular ultrasound and optical coherence tomography for the analysis of the bioresorbable vascular scaffold. Catheter Cardiovasc Interv 2012;79:890–902. Nakatani S, Onuma Y, Ishibashi Y, et al. Temporal evolution of strut light intensity after implantation of bioresorbable polymeric intracoronary scaffolds in the ABSORB Cohort B trial - an application of a new quantitative method based on optical coherence tomography. Circ J 2014;78:1873–81.
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